BACKGROUND: We have previously reported that small synthetic oligopeptides related to human beta-chorionic gonadotropin (beta-hCG) can reduce inflammation. Here we investigated whether such oligopeptides can reduce renal ischaemia-reperfusion injury in the mouse. METHODS: Ten different oligopeptides were administered 1 min before induction of renal ischaemia and 1 min before reperfusion. RESULTS: Survival at 72 h post-reperfusion was significantly higher in mice treated with oligopeptides MTRV, LQG, VLPALPQ or AQGV as compared to placebo-treated mice. Some oligopeptides were more effective than others. AQGV completely prevented mortality and best preserved kidney function. Next, AQGV was tested in a dose-escalating study in a range of 0.3-30 mg/kg. A survival gain was observed with all doses. Improvement of kidney function was observed from 1 mg/kg. Highest survival and best preserved kidney function were observed at 3 and 10 mg/kg. Upon treatment with AQGV, a significantly lower influx of neutrophils was found, apoptosis was decreased, whereas tubular epithelial cell proliferation was significantly increased at 24 h post-reperfusion. Serum levels of TNF-alpha, INF-gamma, IL-6 and IL-10 were significantly decreased at 24 h post-reperfusion. E-selectin mRNA levels in kidneys were significantly decreased at 6 h post-reperfusion. AQGV did not reduce mortality when treatment was started after reperfusion. CONCLUSIONS: This study shows that small oligopeptides related to the primary structure of beta-hCG, especially AQGV, are promising potential drugs for preventing the development of renal ischaemia-reperfusion injury.
BACKGROUND: We have previously reported that small synthetic oligopeptides related to human beta-chorionic gonadotropin (beta-hCG) can reduce inflammation. Here we investigated whether such oligopeptides can reduce renal ischaemia-reperfusion injury in the mouse. METHODS: Ten different oligopeptides were administered 1 min before induction of renal ischaemia and 1 min before reperfusion. RESULTS: Survival at 72 h post-reperfusion was significantly higher in mice treated with oligopeptides MTRV, LQG, VLPALPQ or AQGV as compared to placebo-treated mice. Some oligopeptides were more effective than others. AQGV completely prevented mortality and best preserved kidney function. Next, AQGV was tested in a dose-escalating study in a range of 0.3-30 mg/kg. A survival gain was observed with all doses. Improvement of kidney function was observed from 1 mg/kg. Highest survival and best preserved kidney function were observed at 3 and 10 mg/kg. Upon treatment with AQGV, a significantly lower influx of neutrophils was found, apoptosis was decreased, whereas tubular epithelial cell proliferation was significantly increased at 24 h post-reperfusion. Serum levels of TNF-alpha, INF-gamma, IL-6 and IL-10 were significantly decreased at 24 h post-reperfusion. E-selectin mRNA levels in kidneys were significantly decreased at 6 h post-reperfusion. AQGV did not reduce mortality when treatment was started after reperfusion. CONCLUSIONS: This study shows that small oligopeptides related to the primary structure of beta-hCG, especially AQGV, are promising potential drugs for preventing the development of renal ischaemia-reperfusion injury.
Authors: Faikah Gueler; Nelli Shushakova; Michael Mengel; Katja Hueper; Rongjun Chen; Xiaokun Liu; Joon-Keun Park; Hermann Haller; Gert Wensvoort; Song Rong Journal: PLoS One Date: 2015-01-24 Impact factor: 3.240
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Authors: Roger van Groenendael; Rob Aarnoutse; Matthijs Kox; Lucas van Eijk; Peter Pickkers Journal: Br J Clin Pharmacol Date: 2019-06-02 Impact factor: 4.335
Authors: Roger van Groenendael; Remi Beunders; Jan Hofland; Wim J Morshuis; Matthijs Kox; Lucas T van Eijk; Peter Pickkers Journal: JMIR Res Protoc Date: 2019-02-06
Authors: Janine van der Giessen; Vivian W Huang; C Janneke van der Woude; Gwenny M Fuhler Journal: Clin Transl Gastroenterol Date: 2019-03 Impact factor: 4.488